Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population

• Published in: Scientific reports Vol. 14; no. 1; pp. 9753 - 9
• Main Authors: Lee, Young, Cho, Eun Ju, Choe, Eun Kyung, Kwak, Min-Sun, Yang, Jong In, Oh, Seung-Won, Yim, Jeong Yoon, Chung, Goh Eun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4020/4021; 692/4020/4021/288; Acyltransferases; Adult; Aged; Alleles; Body weight; Case-Control Studies; Fatty liver; Female; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Lipase - genetics; Liver; Liver diseases; Male; Membrane Proteins - genetics; Metabolic fatty liver disease; Metabolism; Middle Aged; multidisciplinary; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - genetics; Obesity; Obesity - genetics; Overweight; Phospholipases A2, Calcium-Independent; Polymorphism, Single Nucleotide; Population studies; Ratios; Republic of Korea - epidemiology; Science; Science (multidisciplinary); Single-nucleotide polymorphism; SNP; Republic of Korea; Genome-wide association study; SNP; Metabolic fatty liver disease
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-60152-0

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD ( P -values, discovery set = 1.60 × 10 –15 and 4.84 × 10 –10 ; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10 –4 , and 7.15 × 10 –4 , odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD ( P -values, discovery set = 2.08 × 10 –8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P -values, 1.515 (1.351–1.700), 1.43 × 10 –12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10 –9 ]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P -values, 1.418 (1.258, 1.600), 1.21 × 10 –8 and 1.225 (1.122, 1.340), 7.06 × 10 –6 , respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.